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Kim, Hangun,Ki, Hyunkyoung,Park, Hee-Sae,Kim, Kwonseop American Society for Biochemistry and Molecular Bi 2005 The Journal of biological chemistry Vol.280 No.23
<P>The enzyme γ-secretase is involved in the cleavage of several type I membrane proteins, such as Notch 1 and amyloid precursor protein. Presenilin-1 (PS-1) is one of the critical integral membrane protein components of the γ-secretase complex and is processed endoproteolytically, generating N- and C-terminal fragments (NTF and CTF, respectively). PS-1 is also known to incorporate into a high molecular weight complex by binding to other γ-secretase components such as Nicastrin, Aph-1, and Pen-2. Mutations on PS-1 can alter the effects of γ-secretase on its many substrates to different extents. Here, we showed that PS-1 mutants have a different activity for Notch cleavage, which depended on the PS-1 mutation site. We demonstrated that defective PS-1 mutants located in CTF, <I>i.e.</I> D385A and C410Y, could restore their γ-secretase activities with the compensatory overexpression of wild type CTF or of minimal deleted CTF (amino acids 349-467). However, the defective PS-1 D257A mutant could not restore their γ-secretase activities with the compensatory overexpression of wild type NTF. In comparison, both D257A NTF and D385A CTF could abolish the γ-secretase activity of wild type and pathogenic PS-1 mutants. We also showed that PS-1 NTF but not CTF forms strong high molecular weight aggregates in SDS-PAGE. Taken together, results have shown that NTF and CTF integrate differently into high molecular weight aggregates and that PS-1 Asp-257 and Asp-385 have different accessibilities in their unendoproteolyzed conformation.</P>
Kim, Hangun,Han, Jeong-Ran,Park, Jaejun,Oh, Minsoo,James, Sarah E,Chang, Sunghoe,Lu, Qun,Lee, Kwang Youl,Ki, Hyunkyoung,Song, Woo-Joo,Kim, Kwonseop American Society for Biochemistry and Molecular Bi 2008 The Journal of biological chemistry Vol.283 No.2
<P>Delta-catenin was first identified through its interaction with Presenilin-1 and has been implicated in the regulation of dendrogenesis and cognitive function. However, the molecular mechanisms by which delta-catenin promotes dendritic morphogenesis were unclear. In this study, we demonstrated delta-catenin interaction with p190RhoGEF, and the importance of Akt1-mediated phosphorylation at Thr-454 residue of delta-catenin in this interaction. We have also found that delta-catenin overexpression decreased the binding between p190RhoGEF and RhoA, and significantly lowered the levels of GTP-RhoA but not those of GTP-Rac1 and -Cdc42. Delta-catenin T454A, a defective form in p190RhoGEF binding, did not decrease the binding between p190RhoGEF and RhoA. Delta-catenin T454A also did not lower GTP-RhoA levels and failed to induce dendrite-like process formation in NIH 3T3 fibroblasts. Furthermore, delta-catenin T454A significantly reduced the length and number of mature mushroom shaped spines in primary hippocampal neurons. These results highlight signaling events in the regulation of delta-catenin-induced dendrogenesis and spine morphogenesis.</P>
Nephrotoxic Potential and Toxicokinetics of Melamine Combined with Cyanuric Acid in Rats
Kim, Ghee Hwan,Kang, Mi Jeong,Noh, Keumhan,Oh, Do Gyeong,Kang, Wonku,Jeong, Hye Gwang,Lee, Kwang Youl,Kim, Hangun,Kim, Hyung Sik,Jeong, Tae Cheon Taylor Francis 2014 Journal of toxicology and environmental health. Pa Vol.77 No.22
( Yongfeng He ),( Hangun Kim ),( Taeyong Ryu ),( Youra Kang ),( Jeong Ae Kim ),( Bo Hyun Kim ),( Jae Hyuk Lee ),( Keonwook Kang ),( Qun Lu ),( Kwonseop Kim ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
This study revealed that CWR22Rv-1 cells overexpressing δ-catenin display bigger tumor formation and higher angiogenic potentials than their matched control cells in the CAM assay. In addition, δ-catenin overexpression in CWR22Rv-1 cells results in increased hypoxia-inducible factor 1-alpha (HIF-1α and vascular endothelial growth factor (VEGF) expression. Furthermore, δ-catenin overexpression was found to enhance nuclear distribution of both β-catenin and HIF-1α in hypoxic condition, which is diminished by knockdown of δ-catenin. Our current study adds novel evidence regarding contribution of δ-catenin to the progression of prostate cancer. ⓒ2012 Federation of European Biochemical Societies. Published by Elsevier B.v.All rights reserved.
20(R)-Ginsenoside Rg3와 20(S)-Ginsenoside Rg3의 HaCaT 세포 이동성과 침윤성에 대한 효과
김상원(Sang-Won Kim),노영찬(Young-Chan Noh),박소연(So-Yeon Park),이미진(Mijin Lee),최희지(Hui-Ji Choi),송규용(Gyu-Yong Song),김항건(Hangun Kim) 대한약학회 2021 약학회지 Vol.65 No.2
Wound healing in the skin is a complex process involving several steps. First is the inflammation stage, in which the wound causes constriction of damaged blood vessels and the aggregation of platelets, aiding neutrophils and macrophages in removing the damaged tissue and preventing infection. This is followed by the proliferation stage involving keratinocytes and fibroblasts. Finally, in the tissue remodeling stage, the wound healing process is completed through contraction of the wound area, which promotes the growth of new tissue. In particular, the migration of keratinocytes and fibroblasts during the proliferation stage to the wound site and penetration of these cells into the surrounding tissues promote the wound healing process. In this study, we performed MTT assays to evaluate the toxicity of 20(R)-Rg3 and 20(S)-Rg3, stereoisomers of ginsenoside Rg3, an active ingredient of Korean ginseng, on the keratinocytes and fibroblasts involved in the proliferation stage. Migration assays, invasion assays, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to assess the expression of genes related to wound healing. We observed that 20(R)-Rg3 was non-toxic and promoted the expression of COL1A2 and ACTC1, genes related to wound healing, thereby increasing the mobility and invasiveness of keratinocytes. In addition, we confirmed that 20(R)-Rg3 increased the initial rate of wound healing in vivo in BALB/c mice. The positive effect of 20(R)-Rg3 on wound healing can be assessed by separating this isomer from 20(S)-Rg3, which has moderate toxicity against keratinocytes and reduces mobility and invasiveness. Thus, 20(R)-Rg3 optical isomers could be potential candidates for the development of effective wound healing medicines.
Improved memory and reduced anxiety in δ-catenin transgenic mice
Ryu, Taeyong,Park, Hyung Joon,Kim, Hangun,Cho, Young-Chang,Kim, Byeong C.,Jo, Jihoon,Seo, Young-Woo,Choi, Won-Seok,Kim, Kwonseop Academic Press 2019 Experimental neurology Vol.318 No.-
<P><B>Abstract</B></P> <P>δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about δ-catenin deficiency mice were performed. However, the effect of δ-catenin overexpression in the brain has not been investigated as yet. Therefore we generated a δ-catenin overexpressing mouse model. To generate a transgenic mouse model overexpressing δ-catenin in the brain, δ-catenin plasmid having a Thy-1 promotor was microinjected in C57BL/6 mice. Our results showed δ-catenin transgenic mice expressed higher levels of N-cadherin, β-catenin, and p120-catenin than did wild type mice. Furthermore, δ-catenin transgenic mice exhibited better object recognition, better sociability, and lower anxiety than wild type mice. However, both mice groups showed a similar pattern in locomotion tests. Although δ-catenin transgenic mice show similar locomotion, they show improved sociability and reduced anxiety. These characteristics are opposite to the symptoms of autism or mental retardation, which are caused when δ-catenin is deficient. These results suggest that δ-catenin may alleviate symptoms of autism, Alzheimer's disease and mental retardation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> δ-Catenin transgenic mice had improved object recognition. </LI> <LI> δ-Catenin transgenic mice showed improved social interactions. </LI> <LI> δ-Catenin transgenic mice showed less anxiety. </LI> </UL> </P>
More, Kunal N.,Lee, Jun Young,Kim, Dong-Yeon,Cho, Nam-Chul,Pyo, Ayoung,Yun, Misun,Kim, Hyeon Sik,Kim, Hangun,Ko, Kwangseok,Park, Jeong-Hoon,Chang, Dong-Jo Elsevier 2018 Bioorganic & medicinal chemistry letters Vol.28 No.5
<P><B>Abstract</B></P> <P>Carbonic anhydrase IX is overexpressed in many solid tumors including hypoxic tumors and is a potential target for cancer therapy and diagnosis. Reported imaging agents targeting CA-IX are successful mostly in clear cell renal carcinoma as SKRC-52 and no candidate was approved yet in clinical trials for imaging of CA-IX. To validate CA-IX as a valid target for imaging of hypoxic tumor, we designed and synthesized novel [<SUP>18</SUP>F]-PET tracer (<B>1</B>) based on acetazolamide which is one of the well-known CA-IX inhibitors and performed imaging study in CA-IX expressing hypoxic tumor model as 4T1 and HT-29 <I>in vivo</I> models other than SKRC-52. [<SUP>18</SUP>F]-acetazolamide (<B>1</B>) was found to be insufficient for the specific accumulation in CA-IX expressing tumor. This study might be useful to understand <I>in vivo</I> behavior of acetazolamide PET tracer and can contribute to the development of successful PET imaging agents targeting CA-IX in future. Additional study is needed to understand the mechanism of poor targeting of CA-IX, as if CA-IX is not reliable as a sole target for imaging of CA-IX expressing hypoxic solid tumors.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Bromopropane Compounds Increase the Stemness of Colorectal Cancer Cells
Cho, Young-Chang,Nguyen, Thanh Thi,Park, So-Yeon,Kim, Kwonseop,Kim, Hyung Sik,Jeong, Hye Gwang,Kim, Kyung Keun,Kim, Hangun MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.9
<P>Bromopropane (BP) compounds, including 1-bromopropane, 2-bromopropane, and 1,2-dibromopropane, are used in industry for various purposes, and their deleterious effects on human health are becoming known. In this study, we examined the effects of BP compounds on the stemness of colorectal cancer cells. At low, non-cytotoxic concentrations, BP compounds significantly increased spheroid formation in CSC221, DLD1, Caco2, and HT29 cells. In addition, the levels of cancer stem cell markers, such as aldehyde dehydrogenase-1, cluster of differentiation 133 (CD133), CD44, Lgr5, Musashi-1, Ephrin receptor, and Bmi-1 increased after exposure to BP compounds. BP compounds increased the transcriptional activity of the TOPflash and glioma-associated oncogene homolog zinc finger protein (Gli) promoters in reporter assays and increased the expression of Gli-1, Gli-2, Smoothened (SMO), and β-catenin by RT-PCR. These results demonstrate for the first time that BP compounds have the potential to promote cancer stemness.</P>
Determination of C-Terminal 관-Catenin Responsible for Inducing Dendritic Morphogenesis.
Lee, Ho-Bin,He, Yongfeng,Yang, Gyeong-Su,Oh, Jin-A,Ha, Ji-Seon,Song, Oh-Hyuen,Lee, Do-Jin,Jung, Sang-Chul,Kim, Kyung Keun,Kim, Kwonseop,Kim, Hangun American Scientific Publishers 2015 Journal of Nanoscience and Nanotechnology Vol.15 No.8
<P>관-Catenin induces dendritic morphogenesis in several cells and it was reported that deletion of C-terminal 207 amino acid of 관-catenin completely abolished the dendritic morphogenesis. However, exact domain responsible for inducing dendritic morphogenesis in C-terminus of 관-catenin was not mapped. Here, we report that expression of ??C47 (lacking 47 amino acid of C-terminus: 1-1200), ??C77 (lacking 77 amino acid of C-terminus: 1-1170) deletion mutants of 관-catenin induced the dendritic morphogenesis of HEK293T and NIH3T3 cells as full-length 관-catenin did. In agreement with previous report, ??C207 deletion mutant did not show the dendritic morphogenesis of the cells. Interestingly, introducing 107 amino acid deletion of C-terminus (??C107 mutant: 1-1140) and 177 amino acid deletion of C-terminus (??C177 mutant: 1-1070) showed limited primary and secondary dendritic process and notable spine-like process formation. These results suggest that 1140-1170 amino acid of C-terminal 관-catenin is required for primary and secondary dendrite-like process formation.</P>